北京大学学报（医学版）最新文献

Kennedy disease is a rare X-linked recessive genetic disease with a low incidence rate. The main manifestations of motor neuron involvement include limb weakness, muscle atrophy, dysarthria, difficulty swallowing, and coughing after drinking water. The patient may die from pulmonary infection and respiratory failure, and there is currently no effective treatment available. There are few reports on anesthesia for such patients and no guidelines or expert consensus. This article reports on perioperative anesthesia management for a 69 years old patient who underwent lumbar spine surgery before with coronary heart disease. The patient was diagnosed with Kennedy disease through electromyography and genetic testing before surgery and underwent knee replacement surgery. After sufficient preoperative consultation and evaluation, femoral nerve block was performed with 0.25% ropivacaine under guidance with ultrasound and nerve stimulator, followed by induction of general anesthesia with sufentanil, propofol, and etomidate. A laryngeal mask was inserted without the use of muscle relaxants and breathing was controlled by machine. During the operation, propofol and remifentanil were used for total intravenous anesthesia. The patient had stable vital signs, well tolerated, and the surgical process was smooth. The time of recovery from anesthesia was short, and no anesthesia related complications, such as nausea, vomiting, aspiration, or suffocation was observed after the operation. Postoperative muscle strength recovery was good. After closely monitoring in the ICU for a day, the patient returned to the regular ward. A postoperative analgesia combination of nerve block and oral nonsteroidal analgesics was performed, and emergency pain rescue with pethidine was administered if necessary. The analgesic effect was satisfactory. The patient was safely discharged in the end and recovered well.

Objective: To evaluate the feasibility of using cell membrane vesicles (CMVs) as a delivery system for small interfering RNA (siRNA) and to assess their performance in a lipopolysaccharide (LPS)-induced inflammatory model of human dental pulp stem cells (DPSCs).

Methods: CMVs were generated from cytochalasin B-treated 3T3 cells and characterized for their physicochemical properties, including morphology, size distribution, and zeta potential, using confocal microscopy and dynamic light scattering. To construct CMVs@siTNF-α, saponin-mediated transient permeabilization was used to facilitate siRNA loading, after which encapsulation efficiency was evaluated by flow cytometry and confocal imaging. Intracellular uptake behaviors were examined using flow cytometry in DPSCs. LPS (1 mg/L) was employed to establish a robust in vitro inflammatory microenvironment. DPSCs were subsequently treated with CMVs or CMVs@siTNF-α, and cell viability was assessed via CCK-8 (cell counting kit-8). The expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbent assay (ELISA) to evaluate both gene-silencing efficiency and downstream anti-inflammatory effects.

Results: CMVs exhibited uniform spherical morphology with an average diameter of approximately 903 nm and a zeta potential of -9.39 mV, confirming successful vesicle formation. CMVs efficiently encapsulated FAM-labeled siRNA, as indicated by a pronounced fluorescence shift in flow cytometry and clear colocalization signals in confocal imaging. DPSCs cultured with CMVs@FAM-siTNF-α demonstrated increased intracellular fluorescence, reflecting efficient vesicle uptake and cytoplasmic siRNA release. Importantly, both CMVs and CMVs@siTNF-α displayed negligible cytotoxicity. LPS stimulation significantly elevated TNF-α, IL-1β, and IL-6 expression, validating the inflammatory model. CMVs alone did not affect cytokine levels, indicating biological inertness. In contrast, CMVs@siTNF-α significantly suppressed the LPS-induced upregulation of TNF-α at both mRNA and protein levels., demonstrating potent gene-silencing activity. Furthermore, suppression of TNF-α led to downstream attenuation of IL-1β and IL-6, with both transcription and secretion significantly decreased compared with the LPS group. These findings collectively confirmed that CMVs enabled efficient intracellular siRNA transport and effectively mitigate inflammatory responses in DPSCs.

Conclusion: CMVs represent a biocompatible and effective siRNA delivery platform capable of achieving robust TNF-α knockdown and ameliorating inflammatory cytokine production in vitro, highlighting their potential for future nucleic acid-based anti-inflammatory therapies.

Objective: To explore the key technical points and value of cell transfer technology in the diagnosis of micro-volume cell fluid.

Methods: In the study, 32 micro-volume cell fluid samples with the diagnosis of tumor or atypical cells in the Department of Pathology, Peking University First Hospital were collected from September 2024 to June 2025. The cells on the ThinPrep cytology test (TCT) slides were divided into several sections and transferred to corresponding slides for immunocytochemistry (ICC) and special staining. Hematoxylin-eosin (HE) staining slides before and after transfer were compared to evaluate the performance of cell transfer technology in maintaining the consistency of cell morphology. The re-diagnosis referring to the results of ICC and special staining of transfer slides were made. The diagnosis before and after cell transfer was compared to evaluate the value of technology in improving the differential diagnostic accuracy.

Results: A total of 140 cell transfer slides were prepared from the 32 samples. Among them, 32 HE-stained slides were consistent with the original TCT slides in terms of staining quality, cell morphology and arrangement, with a success rate of 100%; 99 transfer slides were immuno-stained, of which 91 had accurate color and position of positivity and clear background of negativity, with a success rate of 91.91%; 9 special-stained slides had sharp color contrast and clear background, with a success rate of 100%. With the help of ICC and special staining results of transfer slides, 26 of the 32 samples were accurately diagnosed, including 18 cases of malignant tumors and 8 cases of non-neoplastic lesions; 6 cases remained undiagnosed, including four due to ICC staining failure and two due to too few cells. Compared with the original cytological diagnosis, a definitive differential diagnosis was obtained in 81.25% of cases after cell transfer.

Conclusion: The application of cell transfer technology in TCT samples is feasible in clinical practice and is suitable for cases requiring ICC and special staining for auxiliary diagnosis. It can significantly improve the differential diagnostic accuracy for the micro-volume cell fluid samples, which is invaluable for the special cases which pathological diagnosis can only be made based on the micro-volume cell fluid samples because no more tissue sample is available.

Objective: To preliminarily investigate the effects of direct treatment with cold atmosphere plasma (CAP) on the migration and proliferation capabilities of human gingival fibroblasts (HGFs), as well as the correlation between the doses and the effects.

Methods: The CAP Bio-Med Platform was used to generate the CAP in this study. The characteristics of the CAP source were kept constant by fixing the discharge voltage, frequency, and gas flow rate. Different CAP doses were generated by adjusting the discharge time (20 s, 60 s, 120 s, 180 s) and used to treat HGFs. The temperature, pH, and reactive oxygen species (ROS) levels in the HGFs culture medium were measured following treatment with different CAP doses. The morphology of the HGFs after treatment was observed via immunofluorescence staining, and the cell perimeter and area were calculated. The migration ability of the HGFs after treatment was assessed using a scratch assay, and their proliferation ability was evaluated using a cell counting kit.

Results: As the treatment duration increased, the CAP dose generated by the platform ranged from 0 J to 210.6 J. Different CAP doses did not affect the temperature of the HGFs culture medium. As the CAP dose increased, the pH of the HGFs culture medium first decreased from an initial 8.18±0.06 to 8.13±0.20, then gradually increased to 8.63±0.15 (P < 0.05). The concentration of H₂O₂ in the culture medium peaked at (55.96±1.51) μmol/L in the 60 s CAP treatment group. With an extension in treatment time, the concentration decreased gradually to (22.92±0.57) μmol/L (P < 0.05). Following low-dose CAP treatment (20 s), HGFs exhibited a larger surface area and more pseudopodia extensions. In contrast, following excessively high-dose CAP treatment(180 s), some HGFs displayed a narrow, elongated spindle shape with a smaller surface area than the low-dose group. Compared with the untreated group, low-dose CAP treatment significantly enhanced the migration and proliferation abilities of HGFs (P < 0.05), whereas excessively high-dose CAP treatment inhibited HGFs migration and proliferation (P < 0.05).

Conclusion: Treatment with different doses of CAP alters the pH and ROS levels of the HGFs culture medium. CAP treatment has a dose-dependent effect on the biological behavior of HGFs: Low-dose treatment enhances migration and proliferation, while excessively high-dose treatment inhibits these abilities.

Objective: To clarify the diagnostic efficacy of various diagnostic methods through multi-index combined analysis, and to explore the core diagnostic value of direct immunofluorescence (DIF) in oral mucosal pemphigus vulgaris (PV).

Methods: A total of 53 patients with confirmed oral mucosal PV were included, retrospectively. Their data of DIF, histopathology, serum enzyme-linked immunosorbent assay (ELISA) and clinical diagnosis were systematically analyzed, and diagnostic efficacy of each method was evaluated using indicators, such as sensitivity, specificity, and area under curve (AUC) of the receiver operating characteristic (ROC) curve.

Results: The results showed that among the 53 patients, middle-aged and elderly females were predominant, the buccal mucosa was the most common involved site, and most patients had a history of blistering. The positive rate of DIF was 96.23%, mainly manifested as a reticular fluorescent deposition between epithelial spinous cells, demonstrating the highest diagnostic value with a sensitivity of 96.23%, specificity of 100.00%, and AUC of 0.981. Histopathology ranked second, with a sensitivity of 94.34%, a specificity of 100.00%, and an AUC value of 0.972. The ELISA test had a sensitivity of 82.61%, a specificity of 82.35%, and an AUC value of 0.825. Although the sensitivity of clinical diagnosis was acceptable, its specificity was relatively low. Additionally, DIF exhibited complementarity with histopathology, ELISA, and clinical diagnosis, and combined testing could improve diagnostic accuracy.

Conclusion: DIF is the "gold standard" for the diagnosis of oral mucosal PV. A comprehensive diagnostic workflow of "clinical manifestation-DIF-histopathology-ELISA" is proposed. This integrated diagnostic system not only significantly improves the accuracy of oral mucosal PV diagnosis but also aligns with the core principles of precision medicine, providing a basis for indivi-dualized treatment.

Objective: To compare the clinical outcomes between xenogeneic bone graft materials primarily composed of deproteinized bovine bone mineral (DBBM) and synthetic bone graft materials primarily composed of hydroxyapatite (HA) used in micro crestal flap-alveolar ridge preservation (MCF-ARP) of periodontally compromised molars, so as to provide a reference for their application and promotion.

Methods: In this retrospective case series study, patients who received treatment between October 2024 and April 2025 were enrolled. All the patients underwent MCF-ARP, using either DBBM or HA. Hard tissue changes and alveolar ridge contour collapse were evaluated and compared between the two groups preoperatively and 6 months postoperatively using cone beam computed tomography (CBCT) and intraoral scanning. Soft tissue healing process after the surgery was also assessed.

Results: A total of 14 molars from 14 patients were included. No significant differences were found in hard tissue changes between the two groups 6 months after the surgery (P>0.05). Two weeks and 1 month postoperatively, the vertical collapse of the contour at the ridge center was significantly greater in the HA group compared with the DBBM group [2 weeks: (2.73±1.89) mm vs. (0.00±0.79) mm, P < 0.05; 1 month: (2.74±1.13) mm vs. (0.35±2.34) mm, P < 0.05]. No significant differences were found in other sites at any other follow-up points (P>0.05). In terms of wound healing, the HA group showed a significantly higher percentage of wound area lacking keratinized tissue coverage compared with the DBBM group both 2 weeks and 1 month after the surgery (2 weeks: 47.88%±6.56% vs. 29.43%±14.25%, P < 0.05; 1 month: 25.68%±13.06% vs. 7.19%±7.18%, P < 0.01).

Conclusion: Within the limitations of this study, the analysis suggests that there is no statistically significant difference in hard tissue and alveolar ridge contour parameters 6 months after MCF-ARP following extraction of periodontally compromised molars. However, early soft tissue healing is faster when using DBBM. Future randomized controlled trials with histological analysis are warranted for further validation.

Objective: To propose a novel method for constructing facial smile simulation sequence data based on static three-dimensional (3D) facial data captured at the start and end of smiling, and to preliminarily evaluate the accuracy and feasibility of the proposed method.

Methods: The 3D dynamic facial data of participants transitioning from a neutral expression to a maximum smile were captured using the 3dMD dynamic facial scanning system. A structured 3D face template was deformed and registered to both the smile starting and ending facial data using the Procrustes analysis non-rigid iterative closest point (PA-NICP) registration algorithm developed by our research group, obtaining two sets of structured homologous data. In MATLAB software, the vertex displacements between the corresponding points of the starting and ending homologous datasets were calculated, and intermediate transitional data with a consistent triangular mesh topology were generated through linear interpolation, thereby constructing the facial smile simulation sequence data. The real 3D dynamic facial data captured from the 3dMD system were used as reference data, and the simulation sequence data constructed in this study were used as test data. The 3D morphological deviations between the reference and test data at multiple time points during the smiling process were calculated to evaluate the accuracy of the constructed smile simulation sequence data.

Results: The 3D facial smile simulation sequence data were successfully constructed for one male and one female participants. The average 3D morphological deviation for the simulated sequence of the male participant was (0.31±0.04) mm, and the average 3D morphological deviation for the simulated sequence of the female participant was (0.44±0.08) mm.

Conclusion: Based on the PA-NICP registration algorithm, the construction of facial smile simulation sequence data can be achieved. The intermediate transitional data can be parametrically generated and flexibly adjusted using interpolation functions, providing a novel method for 3D dynamic facial data generation that supports esthetic prosthodontic design, treatment outcome evaluation, and communication between clinicians and patients.

Objective: To investigate the complex association between hemoglobin levels and resting pulse oxygen saturation (SpO₂) among surgical inpatients in a high-altitude environment, and to define precise, gender-specific physiological adaptation thresholds for hemoglobin, thereby providing evidence-based reference values for health management strategies in high-altitude populations.

Methods: This cross-sectional study enrolled adult inpatients from People's Hospital of Xizang Autonomous Region (altitude: 3 650 m) between January 2023 and October 2024. To rigorously evaluate the relationship between hemoglobin and resting SpO₂, multivariate linear regression analysis was performed. Furthermore, restricted cubic spline models and likelihood ratio tests were utilized to explore potential non-linear threshold effects. Models were adjusted for potential confounding factors, including age, body mass index, hypertension, diabetes, smoking, alcoholism, and comorbid pulmonary diseases.

Results: A total of 3 083 inpatients were enrolled in the final analysis, comprising 1 450 males and 1 633 females. The restricted cubic spline analysis revealed a significant non-linear relationship between hemoglobin levels and SpO₂ for the total population (non-linear test, P=0.006), indicating a distinct turning point in the dose-response curve. Two-piecewise linear regression models subsequently identified distinct inflection points for each sex. For female inpatients, the hemoglobin threshold was determined to be 15.482 g/dL; Above this level, SpO₂ significantly decreased as hemoglobin increased (β=-0.477, 95%CI: -0.760 to -0.193, P=0.001). Similarly, for male inpatients, the threshold was identified at 17.288 g/dL; Exceeding this value resulted in a significant inverse correlation between hemoglobin and SpO₂ (β=-0.344, 95%CI: -0.550 to -0.138, P=0.001).

Conclusion: This study establishes specific hemoglobin thresholds for oxygenation status in hospitalized patients at high altitude: 15.482 g/dL for females and 17.288 g/dL for males. Beyond these cut-off values, further increases in hemoglobin are associated with a deterioration in SpO₂, suggesting a transition from physiological adaptation to maladaptive hemoconcentration. These findings highlight the necessity of sex-stratified hemoglobin monitoring and potential preoperative optimization in high-altitude health management to prevent hypoxia-related complications.